The female reproductive cycle is normally a highly periodic process with a cycle length of 28 + 2 days which persists for more than thirty years in most women. Variations in the phase of the reproductive cycle are accompanied by marked changes in the hormonal milieu to which all body tissues are exposed. In particular, estradiol (E2) levels increase 5-10 fold after the occurrence of ovulation. Animal studies have shown a strong interaction between female reproductive cyclicity and the properties of the circadian timing system. Increased E2 levels (endogenous or exogenous) shorten the period of the pacemaker driving the activity-rest cycle. According to our "dual-oscillator" model of the circadian timing system, a significant decrease in the period of the deep oscillator should be associated with a shift in internal phase relations between the temperature and sleep-wake cycles. Using a newly developed technique for unmasking the output of the deep oscillator driving the body temperature cycle, we plan to assess the relationship between circadian and reproductive cyclicity by comparing circadian thermoregulatory and hormonal cycles in normal women during the follicular phase (low E2) and the luteal phase (high E2). We plan to measure the changes in each cyclical system when the other is perturbed (by shift work or irregular menses). We will test the effect of E2 on circadian phase by administering estrogens to post-menopausal women. This work promises to have significant implications for the field of reproductive endocrinology. First, it may demonstrate how monthly changes in gonadal hormones affect the sleep-wake cycle in normal women. Second, it may lead to improvements in the diagnosis and treatment of patients with reproductive cycle abnormalities. Such an intimate relationship between these two cyclic processes would be consistent with recent evidence suggesting that the suprachiasmatic nucleus of the hypothalmus may serve as the pacemaker not only for the periodic sleep-wake cycle, but also for the periodic changes in female reproductive function.